溶栓治疗后急性心肌梗死患者心率变异性的变化

目的观察急性心梗患者(AMI)溶栓后心率变异性(HRV)变化。方法41例患者被分为两组溶栓再通组21例;常规治疗组20例。观察两组患者病后心率变异性的改变。结果溶栓再通组病人在各时间点的HRV均高于常规治疗组(P<0.05);组内比较,3月、6月时的HRV均高于2周时(P<0.05)。2周时再通者室性心律失常低于常规治疗组(P<0.05)。结论溶栓后冠脉再通可改善心脏自主神经系统功能,减少室性心律失常。     

Cytosine deaminase versus thymidine kinase: a comparison of the antitumor activity

The efficacy of single and combination suicide gene therapy was evaluated using a Herpes simplex virus thymidine kinase/ganciclovir system and Escherichia coli cytosine deaminase/5-fluorocytosine system on the rat prostate tumor cell line R3327 AT-1. The wild-type R3327 AT-1 cell line was transfected with a bifunctional fusion gene CDglyTK, which had the advantage that the resulting R3327 AT-1/CDglyTK cell line has the same amount of cytosine deaminase and thymidine kinase molecules. The percentage of viable R3327 AT-1/CDglyTK cells after 96 h incubation with 0.1 micro g/ml ganciclovir or 10 micro g/ml 5-fluorocytosine were 85% and 52% of controls, respectively. The cell viability when both suicide genes systems were activated was 43%. For in vivo analysis, Copenhagen rats were injected subcutaneously with R3327 AT-1 or R3327 AT-1/CDglyTK cells and treated with 30 mg/kg ganciclovir, 500 mg/kg 5-fluorocytosine, or both prodrugs together. A survival of 83% with the thymidine kinase/ganciclovir and 57% with the CD/5-FC could be observed. Only co-administration of thymidine kinase- and cytosine deaminase-specific prodrugs resulted in a 100% recurrence-free survival of the Copenhagen rats with a Dunning R3327 AT-1/CDglyTK prostate tumor and showed an additive cytotoxic effect. Calculation of the degree of activation and the potential of activation can be used to predict the success of a suicide gene therapy. In our case, the cytosine deaminase/5-fluorocytosine system had a low degree of activation (value 40), which is also found in the low response to 5- fluorocytosine in vivo (57% tumor free).     

Exploiting T cell receptor genes for cancer immunotherapy

Adoptive antigen-specific immunotherapy is an attractive concept for the treatment of cancer because it does not require immunocompetence of patients, and the specificity of transferred lymphocytes can be targeted against tumour-associated antigens that are poorly immunogenic and thus fail to effectively trigger autologous T cell responses. As the isolation and in vitro expansion of antigen-specific lymphocytes is difficult, 'conventional' adoptive T cell therapy can only be carried out in specialized centres in small numbers of patients. However, T cell receptor (TCR) genes isolated from antigen-specific T cells can be exploited as generic therapeutic molecules for 'unconventional' antigen-specific immunotherapy. Retroviral TCR gene transfer into patient T cells can readily produce populations of antigen-specific lymphocytes after a single round of polyclonal T cell stimulation. TCR gene modified lymphocytes are functionally competent in vitro, and can have therapeutic efficacy in murine models in vivo. TCR gene expression is stable and modified lymphocytes can develop into memory T cells. Introduction of TCR genes into CD8(+) and CD4(+) lymphocytes provides an opportunity to use the same TCR specificity to produce antigen-specific killer and helper T lymphocytes. Thus, TCR gene therapy provides an attractive strategy to develop antigen-specific immunotherapy with autologous lymphocytes as a generic treatment option.     

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.     

非营养性吸吮联合音乐治疗对新生儿疼痛的缓解作用

目的观察非营养性吸吮（NNS）、音乐治疗（MT）及非营养性吸吮联合音乐治疗（NNS＋MT）在缓解新生儿疼痛中的作用。方法收集2008年1～6月在南京医科大学附属南京儿童医院新生儿医学中心普通新生儿病房收治的新生儿作为研究对象,对符合纳入和排除标准的新生儿按照住院号从小到大顺序分为干预组（NNS亚组、MT亚组、NNS＋MT亚组）和空白对照组,干预措施在新生儿足后跟采血前2min开始持续至研究结束,共15min,空白对照组不予干预措施。通过观察新生儿的心率、经皮氧饱和度（SpO2）及新生儿疼痛行为（NIPS）评分,采集采血针刺前1min、针刺时和针刺后13min过程中的每一分种数据,比较各种干预措施缓解新生儿疼痛的临床效果。采用SPSS11.0软件进行多变量方差分析,ANOVA方差检验,同时应用PostHoc进行组间比较。结果纳入住院新生儿80例,男54例,女26例;各亚组和空白对照组各20例。疼痛刺激后各组的心率均显著加快,于刺激后0～2min达峰值,之后逐渐减慢;NNS亚组与空白对照组心率差异无统计学意义,MT、NNS＋MT亚组与空白对照组心率差异均有统计学意义,MT亚组和NNS＋MT亚组心率差异无统计学意义。疼痛刺激后各亚组SpO2均显著降低,于刺激后2～4min降至最低值,之后逐渐升高;NNS亚组与对照组SpO2差异无统计学意义,MT、NNS＋MT亚组与空白对照组SpO2差异均有统计学意义,MT亚组和NNS＋MT亚组SpO2差异无统计学意义。疼痛刺激后各组NIPS评分均显著提高,于0～1min达峰值,之后逐渐降低,各亚组NIPS评分差异均无统计学意义。与空白对照组比较,MT、NNS＋MT干预措施均可缓解疼痛刺激引起的心率、SpO2和NIPS评分变化。结论新生儿临床医护人员可通过使用MT和NNS＋MT可缓解新生儿疼痛。     

Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy

Little is known about hepatitis C virus (HCV) breakthrough during antiviral therapy, although it would help in understanding HCV resistance to current antiviral treatments. To analyse the implication of virological factors and the vigour of humoral immune responses in this phenomenon, we studied nine chronic hepatitis C patients with a viral breakthrough during IFN/ribavirin combination therapy, as well as five responders and five non-responders. The IRES and regions coding for the capsid protein, the PePHD domain of envelope glycoprotein E2 and the NS5A and 5B proteins were amplified by RT-PCR before treatment, before and during breakthrough, and after treatment. The major variant sequence was obtained by direct sequencing. The heterogeneity of quasispecies was studied by SSCP in all patients and sequencing after cloning in seven genotype 1b-infected patients. Humoral responses against HCV epitopes were also analysed. The major sequences of IRES, PePHD, and NS5B remained stable during treatment, regardless of the treatment response. However, the capsid protein and the regions flanking PePHD showed sequence variations in breakthrough patients, although no specific mutation was identified. The variable V3 region of NS5A, but not the PKR-binding domain and the ISDR, seemed to be associated with differences in response to treatment. The analysis of HCV quasispecies revealed no characteristic pattern during treatment in breakthrough patients, whose HCV genome profiles looked most similar to that of non-responders. The humoral response was similar between groups. In conclusion, viral breakthrough does not seem to be due to selection of resistant strains with signature mutations.     

Radiation therapy for pancreatic cancer: eleven year experience at the JCRT

Radiation therapy (XRT) for 41 patients with unresectable pancreatic cancer resulted in a median survival of 7.0 months. There was no difference in median survival for patients receiving external beam alone (3500 to 5600 cGy) (n = 28), intraoperative (IORT) boost plus external beam (5040 to 6750 cGy) (n = 9), or a gold-198 implant +/- external beam radiation (n = 4). A pilot study using orthovoltage IORT boost indicates no acute toxicity with doses of 1250 to 1750 cGy. Serious late damage has not been observed in any patients followed to 2 years. Local recurrence in patients treated post-operatively after "radical" surgery occurred in one of 10 (10%). This adjuvant treatment is safe and appears to improve local control rates compared to historical data, but survival is still poor. The median survival for the post-operative group is 10 months; three patients are alive without disease 8 months to 8.3 years after treatment.     

Overall results in 304 consecutive patients with acute spontaneous subarachnoid hemorrhage

The results obtained in 304 consecutive patients with spontaneous subarachnoid hemorrhage are described, the majority of whom (86%) were admitted while in acute condition. Only 46% of the patients in this series were in good condition at admission. The initial management was standardized for all patients, but the protocol of "delayed surgery" was applied to patients with subarachnoid hemorrhage from aneurysmal rupture. Two hundred and twenty-two patients (73%) had intracranial aneurysms. Of these, 20 (9%) were moribund and died shortly after admission; nine (4%) underwent emergency surgery due to the coexistence of a life-threatening cerebral hematoma; seven (3%) were operated upon within 3 days of admission; 78 (35%) died after rebleeding or after steady deterioration of the patient's condition due to vasospasm while awaiting surgery. Of the remaining 108 patients ready for delayed surgery, 12 (11%) (operation refused, elderly patients in poor general condition, spontaneous thrombosis of the aneurysm) were treated conservatively, and 96 (89%), who were in various clinical conditions, were actually operated on. Of these 96 patients, 79 (82%) exhibited excellent or good results, 5 (5%) were disabled, and 12 (12%) died. In the authors' experience, the overall management of intracranial aneurysms in unselected patients according to the protocol of delayed surgery results in significant loss of patients awaiting surgery, and good surgical results in the survivors.     

Intravenous and intracoronary fibrinolytic therapy in acute myocardial infarction: Overview of results on mortality, reinfarction and side-effects from 33 randomized controlled trials

During the past 25 years, 24 randomized trials of intravenous(IV) fibrinolytic treatment have been reported, involving atotal of some 6000 patients in the acute phase of myocardialinfarction. Most tested IV streptokinase (SK), but a few testedIV urokinase (UK). In the past 2 or 3 years numerous small randomizedtrials of intracoronary (IC) SK have been started, 9 of which,involving a total of about 1000 such patients have been reported.Because all of these IV and IC trials were small (the largestincluding only 747 patients), their separate results appearcontradictory and unreliable. But, an overview of the data fromthese trials indicates that IV treatment produces a highly significant(22%±5%, (P<0.001) reduction in the odds of death,an even larger reduction in the odds of reinfarction, and anabsolute frequency of serious adverse effects to set againstthis that is much smaller than the absolute mortality reduction.The apparent size of the mortality reduction in the IV trialswas similar whether anticoagulants were compulsory or optional,whether treatment was in a coronary cure unit or an ordinaryward and, surprisingly, whether treatment began early ( <6h from onset of symptoms) or late (generally 12–24 h).In addition, there was no evidence that UK was more effectivethan the less expensive SK, or that, despite their technicalcomplexity, the new IC regimes were more effective than theold IV regimes. Even the IV schedules that have been studied in randomized trialswere, however, quite complex, and the IC schedules were farmore so. Perhaps partly because of this, none of them is widelyused. If so, then some much simpler, and hence more widely practicable,IV SK regimes should be developed and tested. For example, asimple one hour high-dose IV SK infusion, without anticoagulation,will successfully convert virtually all of the available plasminogeninto plasmin. But, it may be several years before the net effectson mortality of any more widely practicable IV SK regimes canbe agreed unless many of the hospitals that do not wish routinelyto use IC regimes or the complex previous IV regimes will collaboratein multicentre randomized trials that can, if necessary, continuerapid intake until some tens of thousands of patients have beenrandomized, and some thousands of deaths have been observedamong the control and treated patients. The same, of course,may be true for any other fibrinolytic regimes (e.g. infusionof tissue plasminogen activator) if their net effects on mortalityare comparable to those of IV SK.